TRANSMISSION OF CREUTZFELDT-JAKOB-DISEASE FROM HUMANS TO TRANSGENIC MICE EXPRESSING CHIMERIC HUMAN-MOUSE PRION PROTEIN
TRANSMISSION OF CREUTZFELDT-JAKOB-DISEASE FROM HUMANS TO TRANSGENIC MICE EXPRESSING CHIMERIC HUMAN-MOUSE PRION PROTEIN
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DOI：
10.1073/pnas.91.21.9936
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发表时间：
1994-10-11
影响因子：
11.1
通讯作者：
PRUSINER, SB
中科院分区：
文献类型：
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作者：
TELLING, GC;SCOTT, M;PRUSINER, SB
构建表达嵌合朊病毒蛋白（PrP）的转基因（Tg）小鼠，其中小鼠（Mo）PrP的片段被相应的人（Hu）PrP序列取代。称为MHu 2 MPrP的嵌合PrP与MoPrP的不同之处在于残基96和167之间的9个氨基酸。所有Tg（MHu 2 M）小鼠在接种三名死于克雅氏病（CJD）患者的脑匀浆后约200天发生神经系统疾病。用CJD朊病毒接种Tg（MHu 2 M）小鼠产生MHu 2 MPrP（Sc）（PrPSc是PrP的羊瘙痒病亚型）;用Mo朊病毒接种产生MoPrPSc。MHu 2 MPrP（Sc）和MoPrPSc在Tg（MHu 2 M）小鼠脑中的蓄积模式不同。约10%的表达HuPrP的Tg（HuPrP）小鼠和非Tg小鼠在接种CJD朊病毒后>500天发生神经系统疾病。Tg（BuPrP）和Tg（MHu 2 M）小鼠对Hu朊病毒的不同亲和性表明朊病毒复制中涉及其他物种特异性因子。诊断，预防和治疗Hu朊病毒疾病应该由Tg（MHu 2 M）小鼠促进。
Transgenic (Tg) mice were constructed that express a chimeric prion protein (PrP) in which a segment of mouse (Mo) PrP was replaced with the corresponding human (Hu) PrP sequence. The chimeric PrP, designated MHu2MPrP, differs from MoPrP by 9 amino acids between residues 96 and 167. All of the Tg(MHu2M) mice developed neurologic disease approximate to 200 days after inoculation with brain homogenates from three patients dying of Creutzfeldt-Jakob disease (CJD). Inoculation of Tg(MHu2M) mice with CJD prions produced MHu2MPrP(Sc) (where PrPSc is the scrapie isoform of PrP); inoculation with Mo prions produced MoPrPSc. The patterns of MHu2MPrP(Sc) and MoPrPSc accumulation in the brains of Tg(MHu2M) mice were different. About 10% of Tg(HuPrP) mice expressing HuPrP and non-Tg mice developed neurologic disease >500 days after inoculation with CJD prions. The different susceptibilities of Tg(BuPrP) and Tg(MHu2M) mice to Hu prions indicate that additional species-specific factors are involved in prion replication. Diagnosis, prevention, and treatment of Hu prion diseases should be facilitated by Tg(MHu2M) mice.